Salvage lenvatinib/everolimus combination therapy after immune checkpoint inhibitor and VEGFR tyrosine kinase inhibitor for metastatic renal cell carcinoma

BackgroundThe optimal treatment for metastatic renal cell carcinoma (mRCC) patients who have progressed after both immune checkpoint inhibitor (ICI) and VEGFR tyrosine kinase inhibitor (TKI) remains uncertain. Lenvatinib and everolimus (LE) are frequently used in combination as salvage therapy because of their different antitumor mechanisms, but efficacy and toxicity data in this setting are lacking.MethodsWe retrospectively reviewed charts from two academic centers for 71 adult mRCC patients who received LE after prior ICI and TKI exposure. We evaluated patient demographics, histology, International mRCC Database Consortium (IMDC) risk group, treatment history, and toxicity details. Outcomes of interest included objective response rate (ORR), time to treatment failure (TTF), overall survival (OS), ≥grade 3 toxicities, and schedule or dosage changes, which were evaluated using descriptive statistics, chi-square test, Cox proportional hazards model, and the Kaplan–Meier method.ResultsThe median age was 64 (range 31–84). Most patients had clear cell histology (84.5%) and had undergone nephrectomy (80.3%). IMDC risks were favorable (19.7%), intermediate (int) (66.2%), poor (11.3%), and unknown (2.8%). The average ORR was 26.8%, while the median TTF was 5.5 months (95% confidence interval [CI], 3.5–7.6) and the median OS was 9 months (95% CI, 7.6–12.9). Intermediate and poor IMDC risks were independently associated with a significantly worse TTF compared to favorable risk (hazard ratio (HR), 3.03, 95% CI, 1.18–7.79), as was ≥4L treatment vs. 2L/3L treatment (HR, 2.02, 95% CI, 1.08–3.8). Of the 71 patients, 57.7% had ≥grade 3 adverse events, 60% had treatment interruption, 44.3% had dose reduction, and 21% stopped treatment due to intolerance.ConclusionsLE therapy is feasible but has modest efficacies following ICI/TKI treatment. Patients with favorable risk or treated earlier may have a better treatment response. These observations need to be confirmed in prospective studies

Testicular Cancer Knowledge and Viewpoints of American Men

INTRODUCTION: We sought to better understand the baseline knowledge and practices of the general population regarding testicular cancer (TC) and testicular self-examination (TSE) in an effort to understand whether current screening guidelines reflect their viewpoint. The U.S. Preventive Services Task Force (USPSTF) currently recommends against TSE for TC screening due to a lack of data to support a benefit. Early detection of TC may reduce the required burden of therapy and associated long-term toxicities. METHODS: This was a cross-sectional survey study. Participants (median age 33 years, IQR 28-39) were recruited via Amazon Mechanical Turk, a validated crowdsourcing platform used to recruit minimally compensated participants. RESULTS: A total of 250 men rated themselves as somewhat unknowledgeable about TC, with no respondents considering themselves very knowledgeable. Only 26.4% of men knew that TC was curable most of the time. Despite 90.8% of men feeling that their doctor had some role in discussing TC/TSE, only 17.2% had discussed these topics with their doctor. Even after being informed of the rationale behind USPSTF recommendations, only 8% of men thought that potential false positives of TSE would be more important than the rare chance of finding early TC. CONCLUSIONS: American men do not feel knowledgeable about TC, have a favorable attitude toward TSE and want their doctor to discuss these topics. Shared decision making regarding TC screening is warranted given the low risk of harm and patient interest, and continued accrual of data on this topic is necessary given the lack of prospective work to date

Urothelial carcinoma involving the distal penis

Urothelial carcinoma (UC) rarely metastasizes to the penis and skin. We report the case of a 73-year-old man with UC metastases to the corpus spongiosum and dermis of the distal penis. We also review the clinicopathologic characteristics and management options for UC metastasizing to the penis. The patient presented with priapism and edema of the genital region. This follows a 5-year history of urothelial carcinoma in situ that progressed to invasive cancer despite intravesical immunotherapy. Seventeen months prior to presentation, the patient underwent a radical cystectomy with adjuvant chemotherapy. The cystectomy specimen demonstrated a pT4a N2 M0 G3 UC and margins were positive for carcinoma in situ. Follow-up had been negative for recurrence until his presentation with priapism. Incisional biopsy of the glans revealed UC and radical penectomy was performed with negative margins. The penile specimen demonstrated extensive involvement of the corpus spongiosum by UC with lymphovascular invasion and subepidermal involvement. Three months after penectomy, the patient presented with inguinal nodal recurrence. Palliative radiotherapy was administered and the patient passed away eight months after surgery

High-Intensity Focused Ultrasound (HIFU) as salvage therapy for radio-recurrent prostate cancer: predictors of disease response

ABSTRACT Background Some men with localized radio-recurrent prostate cancer may benefit from salvage high-intensity focused ultrasound (HIFU). Herein, we describe oncologic outcomes and predictors of disease response after salvage whole gland HIFU from our prospective cohort. Materials and Methods Patients with localized radio-recurrent prostate cancer were prospectively enrolled from January 2005 to December 2014. Participants had to meet both biochemical and histological definitions of recurrence. Exclusion criteria included the receipt of prior salvage therapy, presence of metastatic disease, and administration of ADT in the 6-months prior to enrollment. Participants were treated with a single session of whole-gland HIFU ablation with the AblathermTM device (EDAP, France). The primary endpoint was recurrence-free survival (RFS), defined as a composite endpoint of PSA progression (Phoenix criteria), receipt of any further salvage therapy, receipt of ADT, clinical progression, or death. Kaplan-Meier survival analysis was used to determine the primary end-point and stratifications were used to determine the significance of 6 pre-specified predictors of improved RFS (TRUS biopsy grade, number of study entry TRUS biopsy cores positive, palpable disease at study enrollment, pre-HIFU PSA, an undetectable post-HIFU PSA nadir, and receipt of prior hormone therapy). Survival analysis was performed on participants with a minimum of 1-year follow-up. Results Twenty-four participants were eligible for study inclusion with a median follow-up of 31.0 months. Median PSA at study entry was 4.02ng/ml. Median time to PSA nadir was 3 months after treatment and median post-HIFU PSA nadir was 0.04ng/ml. Median 2-year and 5-year RFS was 66.3% and 51.6% respectively. Of our 6 prespecified predictors, an undetectable PSA nadir was the only significant predictor of improved RFS (HR 0.07, 95% CI 0.02-0.29, log-rank P<0.001). One participant underwent an intervention for a urethral stricture. No participants developed osteitis pubis or rectourethral fistulae. Conclusions Salvage HIFU allows for disease control in selected patients with localized radio-recurrent prostate cancer. An undetectable PSA nadir serves as an early predictor of disease response

High-Intensity Focused Ultrasound (HIFU) as salvage therapy for radio-recurrent prostate cancer: predictors of disease response

<div><p>ABSTRACT Background Some men with localized radio-recurrent prostate cancer may benefit from salvage high-intensity focused ultrasound (HIFU). Herein, we describe oncologic outcomes and predictors of disease response after salvage whole gland HIFU from our prospective cohort. Materials and Methods Patients with localized radio-recurrent prostate cancer were prospectively enrolled from January 2005 to December 2014. Participants had to meet both biochemical and histological definitions of recurrence. Exclusion criteria included the receipt of prior salvage therapy, presence of metastatic disease, and administration of ADT in the 6-months prior to enrollment. Participants were treated with a single session of whole-gland HIFU ablation with the AblathermTM device (EDAP, France). The primary endpoint was recurrence-free survival (RFS), defined as a composite endpoint of PSA progression (Phoenix criteria), receipt of any further salvage therapy, receipt of ADT, clinical progression, or death. Kaplan-Meier survival analysis was used to determine the primary end-point and stratifications were used to determine the significance of 6 pre-specified predictors of improved RFS (TRUS biopsy grade, number of study entry TRUS biopsy cores positive, palpable disease at study enrollment, pre-HIFU PSA, an undetectable post-HIFU PSA nadir, and receipt of prior hormone therapy). Survival analysis was performed on participants with a minimum of 1-year follow-up. Results Twenty-four participants were eligible for study inclusion with a median follow-up of 31.0 months. Median PSA at study entry was 4.02ng/ml. Median time to PSA nadir was 3 months after treatment and median post-HIFU PSA nadir was 0.04ng/ml. Median 2-year and 5-year RFS was 66.3% and 51.6% respectively. Of our 6 prespecified predictors, an undetectable PSA nadir was the only significant predictor of improved RFS (HR 0.07, 95% CI 0.02-0.29, log-rank P<0.001). One participant underwent an intervention for a urethral stricture. No participants developed osteitis pubis or rectourethral fistulae. Conclusions Salvage HIFU allows for disease control in selected patients with localized radio-recurrent prostate cancer. An undetectable PSA nadir serves as an early predictor of disease response.</p></div